The objective of this proposal is to develop techniques which will allow the use of radiolabeled monoclonal antibodies in combination with nuclear medicine imaging for in vivo detection and localization of malignant disease with the ultimate potential of utilizing these reagents to deliver therapeutic doses of 131I in the treatment of these malignancies. Our studies will concentrate on two tumor types (germ cell tumors and melanoma). We plan on utilizing monoclonal antibodies to human hCG which we have already produced and characterized as to their ability to image a human tumor implant without computerized subtraction or enhancement techniques. This agent will be tested as regards radioimaging of testicular nonseminomatous tumors and choriocarcinoma. A second and major thrust will be the development of new monoclonal reagents to tumor associated antigens on testicular cancer cells and malignant melanoma. These monoclonals will be raised to intact human tumor cells (not tumor cell lines) and screening to select appropriate antibodies will be done with freeze stored tumor and normal cells. Once antibodies are selected, their specificity will be characterized by radioimmunoassay against a variety of fresh and frozen malignant and normal human cells and tumor cell lines from various tissues. In addition, immunoperoxidase techniques will be used to examine specificity on histologic sections of normal and malignant tissue from patients. Antibodies with appropriate specificity will be purified and radiolabeled with 131I, undergo safety and molecular integrity screens and then be examined for their ability to image tumors in appropriate patient groups. Reagents which demonstrate adequate localization and radiodosimetry projections will enter Phase I/II testing for radiation therapy (131I) of cancer in appropriate patient groups. The methodology developed should be applicable to a variety of tumor types and may well provide new capabilities in the detection and therapy of cancer.
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